Delirium (acute confusion) frequently complicates the acute illness of elders, resulting in both short- and long- term adverse impacts on health. In recent years, there has been substantial progress in defining and assessing delirium, describing its incidence and prevalence in several clinical populations, identifying its risk factors, and even developing strategies for its prevention. Yet, once delirium occurs, optimal management remains poorly understood. One of the areas of greatest controversy is the use of psychoactive medications in delirious patients. Psychoactive medications are used frequently in this population, either for the management of delirium itself, or for comorbid conditions, such as sleep disorders and pain. While there has been progress in identifying medications as risk factors for incident delirium, the use of medications in established delirium, and their role in its persistence vs. resolution are less well understood. Our proposal involves secondary analysis of data collected in two of the PI's recently completed, NIH-funded studies of delirium. The first, A Trial to Reduce Delirium in Aged Post-acute Patients, enrolled 457 delirious subjects newly admitted to 8 post-acute care facilities. The second, Thinking and Recovery after Cardiac Surgery (TRACS), enrolled 247 subjects aged 60 and older undergoing cardiac surgery at three medical centers, 111 of whom developed delirium. Together, they represent two of the largest prospective cohorts of delirious subjects ever enrolled in research. In addition to performing serial delirium assessments in these studies, we have also completed formal medical record reviews including detailed information on the administration of psychoactive medications. We now propose to use these data to assess the role of major classes of psychoactive medications in the persistence vs. resolution of delirium. We propose the following two Specific Aims and four hypotheses: Aim 1: Using the post-acute dataset, to examine the relationship between exposure to four classes of psychoactive medications: 1) sedative-hypnotics, 2) antipsychotics, 3) anticholinergics, and 4) opioid analgesics, with delirium persistence over a one-month time period. Aim 2: Using patients who developed delirium in the cardiac surgery dataset, to examine the relationship between exposure to the same four classes of psychoactive medications with delirium persistence in the immediate postoperative period. We hypothesize that sedative-hypnotic and anticholinergic medications will be associated with delirium persistence, while antipsychotic medications and opioid analgesics will be associated with delirium resolution. Our proposed aims leverage the resources already invested in assembling and performing longitudinal follow-up on two large cohorts containing hundreds of delirious patients. Our results will inform the medication management of delirium and enable the design of specific evidence-based interventions to treat delirium and improve functional recovery in both acute and post-acute care settings. PUBLIC HEALTH RELEVANCE: Delirium (acute confusion) frequently complicates the acute illness of elders, resulting in both short- and long- term adverse impacts on health. Psychoactive medications are used frequently in delirious patients, either for the management of delirium itself, or for comorbid conditions, such as sleep disorders and pain;yet, whether these medications help to clear delirium or prolong it remains uncertain. Our proposal involves secondary analysis of data collected in two of the PI's recently completed, NIH-funded studies of delirium to assess the role of four major classes of psychoactive medications in the prolongation vs. resolution of delirium. Our results will inform the medication management of delirium and the design of specific evidence-based interventions to treat delirium and improve functional recovery in both acute and post-acute care settings.